Sreekanth Chalasani

Research

A central challenge in neuroscience is to understand how neural circuits in the brain transform environmental stimuli into appropriate behavioral outputs. Identification and functional characterization of each neuron within a circuit remains technically challenging in complex vertebrate brains, but invertebrate organisms offer the advantage of simpler, smaller nervous systems that nonetheless produce diverse and robust behaviors.

The nematode C. elegans provides a unique opportunity to study genes, neurons and neural circuit functions in the whole animals. Removal of food odors activates AWC chemosensory neurons and induces a locomotory search program. We apply a combination of genetics, functional imaging and behavioral analysis to study how this circuit regulates behavior.

We are also interested in extending these studies to the zebrafish larval model.

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Video: Movie showing AWC calcium responses to removal of odor stimulus at 10 sec. The images are false colored such that violet indicates low fluorescence and red and white indicate high fluorescence.

"Our brains respond to changes in our environment with an almost infinite repertoire of
behaviors. I am interested in understanding how neural circuits sense and process information
to generate behaviors."

Our brain contains roughly 100 billion cells,
each connected through thousands of contact
points, adding up to at least a quarter
of a million miles of wiring—enough to reach
from here to the moon. This marvel of evolutionary
engineering allows us to navigate
an ever-changing environment, to learn and
to remember, but its stunning complexity
makes it difficult to trace how information
travels from one neuron to another.
The Chalasani lab uses the nematode Caenorhabditis
elegans (C. elegans), as a model
to understand how neural circuits transform
sensory input into behaviors. Despite its
simplicity, C. elegans displays a number of
sophisticated behaviors, making it an ideal
model to explore how a simple, well-defined
nervous system is able to integrate information
from multiple sensory neurons and remember
it for long periods of time.

The worms spend about 15 minutes searching
for food when they are moved from a
plate with food to a food-free plate. The
duration of this search time is a function of
the quality of the food and the amount of
time they have spent feeding on it before
being moved. The worms are able to learn
the size of a food patch they were growing
on and remember it for at least one hour.
Chalasani and his team have localized the
spatial memory to a pair of interneurons and
identified a crucial role for dopamine signaling
in executing this behavior.

C. elegans neural circuits integrate multiple
sensory inputs to generate complex behaviors.
Chalasani has identified that sensory
neurons use neuropeptides (small signaling
molecules) to communicate information
about the identity and strength of the
sensory stimuli to the rest of the nervous
system. Neuropeptide signaling represents a
new approach for coding sensory information
in the brain.

He and his group have also observed an interesting
predator-prey relationship between
C. elegans and a larger worm called Pristionchus
pacificus. They found that C. elegans
uses three previously undefined sensory
neurons to detect and avoid predators and
their secretions. Surprisingly, pre-treating
the worm with human anti-anxiety drugs
attenuates its response to the predator.

In the future, Chalasani plans to extend
his lab's studies to zebrafish larvae to test
whether vertebrate and invertebrate circuits
use similar mechanisms to process information,
hoping to gain new insight into how the
human brain functions.